The focus of our research program is to understand the role of cell adherence and cell signaling in human oral biofilms. Oral streptococci and actinomyces form the majority of gram-positive early colonizers on a clean tooth surface. The major gram-negative bacterium is Fusobacterium nucleatum. Members of each of these groups and 13 other genera of oral bacteria were examined for their ability to bind to Helicobacter pylori, a major causative agent of chronic gastritis. Only F. nucleatum recognized H. pylori; the interaction was inhibitable by lactose: the fusobacterial cell appeared to possess the adhesin, while the helicobacter expressed a corresponding receptor. These results give credence to the notion that dental plaque may serve as a reservoir for this pathogen outside of the stomach. The adherence-relevant sca operon of Streptococcus gordonii DL1 contains three genes. By sequence homologies with other ATP-binding cassette systems for transport of small molecules, the gene products are an ATPase, a hydrophobic membrane protein and a substrate-binding lipoprotein. Insertional mutations in the genes encoding the ATPase (scaC) and the substrate-binding lipoprotein (scaA) resulted in impaired growth of cells in media containing <0.5 uM Mn2+ and >70% inhibition of 54Mn2+ uptake. Production of ScaA lipoprotein was induced at low extracellular Mn2+ (<0.5 uM) and by addition of =20 uM Zn2+. ScaA is a high-affinity binding lipoprotein for acquisition of Mn2+ and is essential for growth of streptococci under Mn2+-limiting conditions like that found in the oral cavity. S. gordonii DL1 and other genetically distinct streptococci participate in lactose-inhibitable cell-to-cell interactions called intrageneric coaggregations. A transposon insertion mutant was identified that failed to exhibit lactose-inhibitable intrageneric coaggregations but remained capable of other intergeneric coaggregations with actinomyces. A 6.5-kb region containing the transposon insertion site near the 5' end was sequenced and contained sequence homologies to proteins involved in transport of disaccharides lactose and cellobiose. These results suggest that the lactose-inhibitable intrageneric coaggregations may be mediated by dual functional surface proteins that also transport disaccharides. The long range goal of these studies, collectively, is to elucidate the molecular mechanisms involved in cross talk among the bacteria as they colonize the human oral ecosystem. Our intention is to extend the studies of cell-to-cell contact to include gene expression after accretion into the biofilm.